Department of Biochemistry and Cell Biology
Kevin R. MacKenzie
Structure, stability and folding of
integral membrane proteins
Although integral membrane proteins comprise perhaps 30% of open reading frames in genomes, they represent fewer than 1% of the entries in the Protein Data Bank. Efforts in the lab are focused on identifying biologically important transmembrane domain interactions that are amenable to biophysical and biochemical analysis; T cell signaling is one area of interest. Structures of complexes of a-helices determined by solution NMR will reveal the types of interactions that stabilize such oligomers. Qualitative and quantitative measures of helix-helix association constants will be obtained using in vivo and in vitro assays. Mutagenesis experiments will test the sequence dependence of these interactions. A similar approach has led to a model for the dimerization of the transmembrane domain of glycophorin A that was used to increase the stability and specificity of this dimer by rational design of an inter-helical hydrogen bond.
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